In the fields of medicine (search for a novel biomarker, elucidation of disease mechanisms), pharmacology (application to pharmacokinetics/safety testing), engineering (application to materials development/deterioration analysis (organic EL, liquid crystal, solar batteries)), agriculture (detection of foreign substances (food safety testing), species improvement) and the like, samples are ionized and the generated ions are subjected to mass spectroscopy. In the case wherein a sample, such as of a drug or a peptide, is analyzed, a MALDI mass spectrometer having an atmospheric pressure MALDI ion source, a quadrupole ion trap, a time-of-flight mass spectrometer (TOFMS) and/or the like is used (see Patent Document 1). In such an atmospheric pressure MALDI mass spectrometer, ions generated in an atmospheric pressure MALDI ion source are captured by a quadrupole ion trap so as to be dissociated in multiple stages if necessary and are subjected to mass spectroscopy by a TOFMS.
FIG. 6 is a diagram showing the entire configuration of an atmospheric pressure MALDI mass spectrometer. Here, the X direction is one direction parallel to the ground, the Y direction is the direction perpendicular to the X direction and parallel to the ground, and the Z direction is the direction perpendicular to the X direction and the Y direction.
An atmospheric pressure MALDI mass spectrometer 201 is formed of an ionization chamber 210 for ionizing a sample S under atmospheric pressure (105 Pa, for example), and a mass spectroscopy unit 20 for detecting ions that have been introduced from the ionization chamber 210 in a high vacuum atmosphere (10−3 Pa to 10−4 Pa, for example).
The mass spectroscopy unit 20 is equipped with a first middle vacuum chamber 21 that is adjacent to the ionization chamber 210, a second middle vacuum chamber 22 that is adjacent to the first middle vacuum chamber 21 and an analysis chamber 23 that is adjacent to the second middle vacuum chamber 22. In addition, the inside of the housing of the ionization chamber 210 is at atmospheric pressure (105 Pa, for example), the inside of the first middle vacuum chamber 21 is vacuumed to a low vacuum state (102 Pa, for example) by means of a rotary pump 26, the inside of the second middle vacuum chamber 22 is vacuumed to a middle vacuum state (10−1 Pa to 10−2 Pa, for example) by means of a turbo molecular pump 25, and the inside of the analysis chamber 23 is vacuumed to a high vacuum state (10−3 Pa to 10−4 Pa, for example) by means of a turbo molecular pump 25. That is to say, the atmospheric pressure MALDI mass spectrometer 201 forms a multi-stage differential vacuum system wherein the degree of vacuum can be increased step by step from the ionization chamber 210 towards the analysis chamber 23.
The ionization chamber 210 is provided with a chamber 11 (housing) in a rectangular parallelepiped form (width of 60 cm×depth of 60 cm×height of 80 cm, for example), a sample stage 50, an optical microscope 30 and a laser light source 41. As a result, a space is created inside of the chamber 11.
The lower surface inside of the chamber 11 is equipped with the sample stage 50. The sample stage 50 is provided with a sample table in a block form on which a sample S is mounted and a drive mechanism for driving the sample table in the X direction, the Y direction, and the Z direction.
The optical microscope 30 is placed inside the chamber 11 to the left. The optical microscope 30 is provided with a light source unit 31 for reflecting illumination and an image acquisition device 33 installed inside of the chamber 11 at the top, and a light source unit 32 for transmitted illumination placed inside of the chamber 11 at the bottom.
In such an optical microscope 30, a region set on a sample S placed at a predetermined observation point P1 by means of a sample stage 50 is illuminated with a light emitted from a light source unit 31 for reflecting illumination in the −Z direction. Thus, the light reflected from the region set on the sample S in the Z direction is led to the image acquisition device 33. In addition, the region set on the sample S placed at the predetermined observation point P1 by means of the sample stage 50 is illuminated with a light emitted from alight source unit 32 for transmitted illumination in the Z direction. Thus, the light that has transmitted through the region set on the sample S in the Z direction is led to the image acquisition device 33. As a result, the image acquisition device 33 displays an enlarged image of the region set on the sample S on a monitor, or the like, on the basis of the detected light. Thus, an operator can determine the analysis point (specified point) on the sample S while observing the enlarged image of the region set on the sample S. In addition, the computer allows the sample stage 50 to shift the sample S from the observation point P1 to the ionization point P2 on the basis of the information with which the analysis point (specified point) has been determined. Here, the usage of the light source unit 31 for reflecting illumination and/or of the light source unit 32 for transmitted illumination is selected depending on the transmittances of the substrate and the sample S.
In addition, a laser light source 41 for emitting a laser beam L in pulse form is installed in the upper right portion of the chamber 11 so that a matrix-assisted laser desorption/ionization method can be implemented.
Furthermore, a heater block with a built-in temperature adjusting mechanism is fixed to the right sidewall of the chamber 11. An introduction pipe 12 in a circular pipe form is created in the heater block and the inside of the chamber 11 communicates with the inside of the first middle vacuum chamber 21 via the introduction pipe 12. Here, the introduction pipe 12 is in an L shape and is arranged in such a manner that the inlet faces downwards (−Z direction) and the outlet faces to the right (X direction) inside of the first middle vacuum chamber 21.
In this ionization chamber 210, the analysis point on the sample S, which is placed at the predetermined ionization point P2 by means of the sample stage 50, is irradiated from above by the laser beam L emitted from the laser light source 41. When the analysis point on the sample S is irradiated with the laser beam L, the target substance at the analysis point on the sample S is rapidly heated, vaporized and ionized. At this time, the air present inside of the chamber 11 flows into the first middle vacuum chamber 21 through the introduction pipe 12 due to the difference in pressure between the inside of the chamber 11 and the inside of the first middle vacuum chamber 21. The ions generated inside of the chamber 11 are also drawn into the introduction pipe 12 by riding on this airflow and are discharged into the first middle vacuum chamber 21.
A first ion lens is provided inside of the first middle vacuum chamber 21. The electrical field generated by the first ion lens helps the ions to be drawn into the introduction pipe 12 and, at the same time, converges the ions.
A three-dimensional quadrupole-type ion trap made up of one annular ring electrode and a pair of end cap electrodes arranged so as to face each other and sandwiching the ring electrode is provided inside of the second middle vacuum chamber 22. Thus, the ions that have been introduced into the second middle vacuum chamber 22 are sent into the analysis chamber 23 by the three-dimensional quadrupole-type ion trap.
A flight pipe and an ion detector 24 are provided inside of the analysis chamber 23. Thus, ions having a predetermined mass (strictly speaking, mass-to-charge ratio m/z) pass through the space in the flight pipe during a predetermined period of time. The ions that have passed through the flight pipe reach the ion detector 24, and the ion detector 24 outputs an ion intensity signal, depending on the amount of ions that has been reached, as a detection signal.